New evidence on the controversy over the correlation between vertebral osteoporosis and intervertebral disc degeneration: a systematic review of relevant animal studies.

OBJECTIVE: The effect of vertebral osteoporosis on disc degeneration remains controversial. The aim of this study was to conduct a systematic review and meta-analysis of relevant animal studies to shed more light on the effects and mechanisms of vertebral osteoporosis on disc degeneration and to promote the resolution of the controversy. METHODS: The PubMed, Cochrane Library, and Embase databases were searched for studies that met the inclusion criteria. Basic information and data were extracted from the included studies and data were analyzed using STATA 15.1 software. This study was registered on INPLASY with the registration number INPLASY202370099 and https://doi.org/10.37766/inplasy2023.7.0099 . RESULTS: A total of 13 studies were included in our study. Both animals, rats and mice, were covered. Meta-analysis results showed in disc height index (DHI) (P < 0.001), histological score (P < 0.001), number of osteoblasts in the endplate (P = 0.043), number of osteoclasts in the endplate (P < 0.001), type I collagen (P < 0.001), type II collagen (P < 0.001), aggrecan (P < 0.001), recombinant a disintegrin and metalloproteinase with thrombospondin-4 (ADAMTS-4) (P < 0.001), matrix metalloproteinase-1 (MMP-1) (P < 0.001), MMP-3 (P < 0.001), MMP-13 (P < 0.001), the difference between the osteoporosis group and the control group was statistically significant. In terms of disc volume, the difference between the osteoporosis group and the control group was not statistically significant (P = 0.459). CONCLUSION: Our study shows that vertebral osteoporosis may exacerbate disc degeneration. Abnormal bone remodeling caused by vertebral osteoporosis disrupts the structural integrity of the endplate, leading to impaired nutrient supply to the disc, increased expression of catabolic factors, and decreased levels of type II collagen and aggrecan may be one of the potential mechanisms.

Effect of basal metabolic rate on rheumatoid arthritis: a Mendelian randomization study.

PURPOSE: Basal metabolic rate (BMR) as one of the most basic and significant indicators of metabolism has been associated with human health. Previous studies showed that the development of rheumatoid arthritis (RA) is linked to BMR; however, the causal relationship between BMR and RA is unknown. Thus, we aimed to explore the causal relationship between BMR and RA as well as RA-related factors. METHODS: Mendelian randomization (MR) analysis was performed on collected genome-wide association studies information. The effect of horizontal pleiotropy was detected by MR-PRESSO and MR-Radial. Five MR analysis methods were applied, including inverse variance weighted, MR-Egger, weighted median, weighted mode, and simple mode. Four sensitivity analysis methods were used for the validation of the significant MR analysis results. A two-component mixture of regressions method was additionally used to validate single nucleotide polymorphisms and to verify results. RESULTS: Genetically, there is a causal effect of BMR on overall RA (odds ratio = 1.25, 95% confidence interval: 1.07-1.47, PIVW = .006), seropositive RA (odds ratio = 1.20, 95% confidence interval: 1.01-1.44, PIVW = .035), and seronegative RA (odds ratio = 1.36, 95% confidence interval: 1.04-1.78, PIVW = .023). Sensitivity analyses validated the robustness of the above associations. No evidence supported the effect of RA on BMR. Moreover, BMR showed no causal relationship with rheumatoid factor, C-reactive protein, erythrocyte sedimentation rate, interleukin-1ß, tumor necrosis factor-α, and matrix metallopeptidase 3. CONCLUSION: MR results implied the causal effect of BMR on RA and raised our attention to the importance of BMR in RA's pathology.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

Efficacy and safety of perioperative use of non-steroidal anti-inflammatory drugs for preemptive analgesia in lumbar spine surgery: a systematic review and meta-analysis.

OBJECTIVE: Lumbar spine disorders have become an increasingly common health problem in recent years. Modern clinical studies have shown that perioperative analgesia at certain doses can reduce postoperative pain by inhibiting the process of peripheral sensitization and central sensitization, which is also known as "preemptive analgesia," Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs that achieve antipyretic and analgesic effects by inhibiting cyclooxygenase (COX) and affecting the production of prostaglandins. Our meta-analysis aimed to assess the efficacy and safety of perioperative preemptive analgesia with non-steroidal anti-inflammatory drugs in patients with lumbar spine surgery. METHODS: We searched PubMed, ScienceDirect, the Cochrane Library, and the Web of Science for randomized controlled trials (RCTs) that met the inclusion criteria. A total of 12 clinical studies were included to assess the efficacy and safety of perioperative NSAIDs preemptive analgesia for lumbar spine surgery. RESULT: Twelve studies, including 845 patients, met the inclusion criteria. The results showed that perioperative receipt of NSAIDs for preemptive analgesia was effective and safe. Patient's postoperative morphine consumption (P < 0.05), visual analog scale (P < 0.05), and numerical rating scale (P < 0.05) were not statistically associated with postoperative complications (P > 0.05). CONCLUSION: Our findings suggest that NSAIDs are effective and safe for preemptive analgesia in the perioperative period of lumbar spine surgery and that more and better quality RCTs and more in-depth studies of pain mechanics are still needed.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

Does vertebral osteoporosis delay or accelerate lumbar disc degeneration? A systematic review.

The effect of vertebral osteoporosis on disc degeneration is still debated. The purpose of this study was to provide a systematic review of studies in this area to further reveal the relationship between the two. Relevant studies were searched in electronic databases, and studies were screened according to inclusion and exclusion criteria, and finally, basic information of the included studies was extracted and summarized. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 34 publications spanning 24 years were included in our study. There were 19 clinical studies, including 12 prospective studies and 7 retrospective studies. Of these, 7 considered vertebral osteoporosis to be positively correlated with disc degeneration, 8 considered them to be negatively correlated, and 4 considered them to be uncorrelated. Two cadaveric studies were included, one considered the two to be negatively correlated and one considered them not to be correlated. Seven animal studies were included, of which five considered a positive correlation between vertebral osteoporosis and disc degeneration and two considered a negative correlation between the two. There were also 6 studies that used anti-osteoporosis drugs for intervention, all of them were animal studies. Five of them concluded that vertebral osteoporosis was positively associated with disc degeneration, and the remaining one concluded that there was no correlation between the two. Our systematic review shows that the majority of studies currently consider an association between vertebral osteoporosis and disc degeneration, but there is still a huge disagreement whether this association is positive or negative. Differences in observation time and follow-up time may be one of the reasons for the disagreement. A large number of clinical and basic studies are still needed in the future to further explore the relationship between the two.

DJ-1-mediated p62 degradation delays intervertebral disc degeneration by inhibiting apoptosis of nucleus pulposus cells.

Intervertebral disc degeneration (IDD) is the most important pathological basis of degenerative spinal diseases, for which effective interventions are still lacking. Oxidative stress is considered to be one of the leading pathological mechanisms contributing to IDD. However, the exact role of DJ-1 as an essential member of the antioxidant defense system in IDD is still unclear. Therefore, the aim of this study was to investigate the role played by DJ-1 in IDD and to reveal its potential molecular mechanisms. Western blot and immunohistochemical staining assays were performed to detect the expression of DJ-1 in degenerative nucleus pulposus cells (NPCs). After overexpression of DJ-1 in NPCs by lentiviral transfection, DCFH-DA and MitoSOX fluorescent probes were used to evaluate the levels of reactive oxygen species (ROS); while western blot, TUNEL staining, and Caspase-3 activity were used to assess apoptosis. Immunofluorescence staining was used to demonstrate the relationship between DJ-1 and p62. After inhibition of lysosomal degradation function with chloroquine, p62 degradation and apoptosis in DJ-1 overexpressing NPCs were further examined. In vivo, we assessed the therapeutic effect of upregulated DJ-1 on IDD by X-ray, MRI and Safranin O-Fast green staining. The protein expression of DJ-1 was significantly decreased in degenerated NPCs, accompanied by increased apoptosis. However, overexpression of DJ-1 significantly inhibited the elevated ROS levels and apoptosis in NPCs under oxidative stress. Mechanistically, our results showed that upregulation of DJ-1 promoted p62 degradation via the autophagic lysosomal pathway and that the protective effect of DJ-1 on NPCs under oxidative stress was partially mediated by promoting lysosomal pathway degradation of p62. Moreover, intradiscal injection of adeno-associated virus for overexpression of DJ-1 mitigated the progression of IDD in rats. This study reveals that DJ-1 maintains the homeostasis of NPCs by promoting the degradation of p62 through the autophagic lysosomal pathway, suggesting that DJ-1 is a promising new target for IDD intervention.

Is coronal imbalance in degenerative lumbar scoliosis patients associated with the number of degenerated discs? A retrospective imaging cross-sectional study.

BACKGROUND: Degenerative lumbar scoliosis (DLS) is a common degenerative disease of the spine, that predominates in the elderly, and causes spinal deformities along with severe pain and reduced quality of life. The relationship between DLS and degenerated discs is now a new direction of research. Our study aimed to the relationship between the imaging parameters of coronal imbalance and the number of degenerated discs in patients with degenerative lumbar scoliosis and analyzed the segmental distribution of the degenerated discs in patients with DLS. METHODS: We performed a retrospective analysis of the imaging of 40 patients who met the inclusion criteria who attended our outpatient clinic between April 2021 and July 2021, measuring the intervertebral space height of the AV (high side and low side), Cobb angle, and AVT (Apical vertebral translation) from coronal X-ray. Degenerated discs were evaluated by the Pfirrmann score based on T2-weighted magnetic resonance images. We record the number of degenerated discs (Graded as Grade III, Grade IV or Grade V by the Pfirrmann score) and the segments in which they are located. Finally, we explore the relationship between the imaging parameters of coronal imbalance and the number of degenerated discs in patients with DLS. RESULT: Among the 40 patients with DLS in our study, all patients had degenerated discs in the lumbar spine, 95% of patients had degenerated discs(Pfirrmann score Grade III, Grade IV or Grade V) in 2 or more segments, with the L4-L5 segment being the most involved segment with the most degenerated discs, followed by the L3-L4 segment and the L5-S1 segment. There was no statistically significant relationship between the number of degenerated discs and the coronal imbalance in patients with DLS. CONCLUSION: Our results showed an association between DLS and degenerated discs, but there was no statistically significant relationship between imbalance in the coronal plane of the lumbar spine and the number of degenerated discs in patients with DLS. The distribution of degenerated disc segments in patients with DLS showed a higher likelihood of disc degeneration in 2 or more segments, and a higher frequency of disc degeneration in the inferior disc and in the adjacent segments of the AV.

Identification of kaempferol as an OSX upregulator by network pharmacology-based analysis of qianggu Capsule for osteoporosis.

Osteoporosis is the most common metabolic disease of skeleton with reduced bone density and weaker bone. Qianggu Capsule as a traditional chinese medicine has been widely used to treat osteoporosis. The potential pharmacological mechanism of its active ingredient Gusuibu is not well understood. The purpose of this work is to analyze the anti-osteoporosis function of Gusuibu based on network pharmacology, and further explore the potential mechanism of Qianggu Capsule. The active compounds and their corresponding targets of Gusuibu were obtained from TCMSP, TCMID, and BATMAN-TCM databases. Potential therapeutic targets for osteoporosis were obtained through DisGeNET, TTD, GeneCards, MalaCards, CTD, and OMIM databases. The overlapping targets of Gusuibu and osteoporosis were obtained. GO and KEGG pathway enrichment analysis were performed. The "Gusuibu-active compounds-target genes-osteoporosis" network and protein-protein interaction (PPI) network were constructed, and the top hub genes were screened by using the plug-in CytoHubba. Molecular docking was used to verify the binding activity of hub genes and key compounds. We identified 21 active compounds and 140 potential therapeutic targets that may be related to Gusuibu and 10 hub genes (AKT1, IL6, JUN, TNF, MAPK3, VEGFA, EGFR, MAPK1, CASP3, PTGS2). Molecular docking analysis demonstrated that four key active small molecules in Gusuibu (including Luteolin, Naringenin, Kaempferol, and Beta-sitosterol) have excellent binding affinity to the target proteins encoded by the top 10 hub genes. Our new findings indicated that one key active compound kaempferol activated the expression of osteoblast specific transcription factor OSX through JNK kinase pathway.

Evaluation of the Efficacy of Stem Cell Therapy in Animal Models of Intervertebral Disc Degeneration Based on Imaging Indicators: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to make a systematic review of the therapeutic effect of stem cells in animal models of disc degeneration from an imaging point of view. Methods: Data were extracted by searching electronic databases for RCTs that met the inclusion criteria. Data analysis was performed using RevMan 5.3 and STATA 15.1 software. This meta-analysis was registered with INPLASY, registration number INPLASY202240148. Results: A total of 34 studies were included, covering four species of animals, rabbits, sheep, rats, and mice, with a total of 1163 intervertebral discs. In terms of DHI, the efficacy of stem cell group in rabbits (P < 0.001), mice (P < 0.001), sheep (P < 0.001), and rats (P = 0.001) was better than that in control group. In terms of disc height, the efficacy of stem cell group in rats (P < 0.001) was better than that in control group, while in sheep (P = 0.355), there was no statistical difference between two groups. In terms of MRI index, the efficacy of stem cell group in rats (P < 0.001), mice (P < 0.001), and rabbits (P = 0.016) was better than that in control group. In terms of MRI signal score, the efficacy of stem cell group in rabbits (P < 0.001) was better than that of control group. In terms of T2 signal intensity, stem cell group was more effective than control group in rabbits (P < 0.001), mice (P < 0.001), and rats (P = 0.003). Conclusion: Stem cell therapy can improve intervertebral disc-related imaging parameters in animal models of disc degeneration, indicating that stem cell therapy has a repairing effect on intervertebral discs. However, given the heterogeneity and limitations of this study, this conclusion still needs to be tested by a large number of studies.

Meta-Analysis of the Efficacy and Safety of Alendronate Combined with Atorvastatin in the Treatment of Osteoporosis in Diabetes Mellitus.

OBJECTIVE: Diabetes is a chronic disease caused by defective insulin secretion in the body, resulting in metabolic abnormalities with persistent blood glucose elevation. Osteoporosis is the most common diabetes complication. The aim of this study was to perform a meta-analysis of the effects of alendronate combined with atorvastatin compared with alendronate alone in the treatment of osteoporosis in diabetes mellitus. METHODS: Two researchers independently used PubMed, ScienceDirect, Cochrane Library, Wanfang Data, CNKI, and VIP databases to search for all relevant studies that met the inclusion criteria and used RevMan 5.3 and STATA 16.0 for data analysis. RESULTS: Fourteen studies that met the inclusion criteria were selected, including 1456 patients. Among the data extracted in this meta-analysis, bone mineral density (BMD) was the primary outcome measurement, while total effective rate, VAS, osteoprotegerin (OPG), bone Gla protein (BGP), bone alkaline phosphatase (BAP), blood P and Ca, and adverse effects were secondary outcome measurements. Our results showed that alendronate combined with atorvastatin is more effective than alendronate alone, with higher BMD, OPG, BGP, and BAP, more significant pain relief, and fewer adverse events. CONCLUSION: The results of this meta-analysis indicate that alendronate combined with atorvastatin is a better treatment for osteoporosis in diabetes mellitus, showing more effective and higher BMD and fewer adverse events than alendronate alone.

Evaluation of the Efficacy of Stem Cell Therapy in Ovariectomized Osteoporotic Rats Based on Micro-CT and Dual-Energy X-Ray Absorptiometry: A Systematic Review and Meta-Analysis.

OBJECTIVE: Osteoporosis is an abnormal bone metabolism disease characterized by microstructural degeneration of bone tissue and reduction in bone mass, resulting in increased brittleness of bone tissue and susceptibility to fracture. Due to the tissue regenerative potential of stem cell transplantation, it is now used in the treatment of various disease models such as osteoporosis. The purpose of this work is to carry out a systematic review and meta-analysis of the efficacy of stem cell therapy in ovariectomized (OVX) osteoporotic rats. METHODS: PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang Databases were used to search for articles that met the inclusion criteria. Two researchers independently screened the articles that met the inclusion criteria. RevMan 5.3 and STATA 16.0 were used for data analysis. This meta-analysis was registered at INPLASY with reference number ID: INPLASY202150017. RESULTS: Thirteen eligible studies were selected, including 405 rats. The sources of stem cells are divided into four main categories: bone marrow mesenchymal stem cells (BMSCs), adipose-derived stem cells (ADSCs), amniotic membrane mesenchymal stem cells (AM-MSCs), and human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs). Compared with the OVX group, both stem cell transplantation groups had higher bone mineral density (BMD) (BMSCs: SMD = 2.01, 95% CI: [1.38, 2.63], P < 0.001, I 2 = 76.6%; ADSCs: SMD = 2.24, 95% CI: [0.79, 3.69], P = 0.003, I 2 = 86.7%) and bone volume/total volume (BV/TV) (hUCB-MSCs: SMD = 1.71, 95% CI: [0.97, 2.44], P < 0.001, I 2 = 0%; ADSCs: SMD = 2.16, 95% CI: [0.27, 4.04], P = 0.025, I 2 = 82.6%). In the BMSC treatment groups, the trabecular numbers (Tb.N) (SMD = 4.28, 95% CI: [0.91, 7.64], P = 0.013, I 2 = 94.9%) were significantly higher, whereas the results for trabecular thickness (Tb.Th) (SMD = 2.7, 95% CI: [-0.34, 5.73], P = 0.081, I 2 = 95.4%) and trabecular spacing (Tb.Sp) (SMD = -3.08, 95% CI: [-6.55, 0.38], P = 0.081, I 2 = 96.3%) were not statistically significant compared to those of the OVX group. The stem cell transplantation group had a low BMD, BV/TV, and Tb.N compared to the sham operation group. CONCLUSION: Stem cell therapy may increase bone strength, bone volume, and the number of trabeculae in OVX osteoporotic rats. The results of this meta-analysis showed the potential therapeutic effect of stem cell transplantation in OVX osteoporotic rats, bringing new therapeutic ideas and directions to the clinical treatment of osteoporosis. Due to the limited number and quality of studies related to some outcomes, more high-quality RCTs are still needed in the future to complement the existing findings.

Sirtuins: Potential Therapeutic Targets for Defense against Oxidative Stress in Spinal Cord Injury.

Spinal cord injury (SCI) is one of the most incapacitating neurological disorders. It involves complex pathological processes that include a primary injury and a secondary injury phase, or a delayed stage, which follows the primary injury and contributes to the aggravation of the SCI pathology. Oxidative stress, a key pathophysiological event after SCI, contributes to a cascade of inflammation, excitotoxicity, neuronal and glial apoptosis, and other processes during the secondary injury phase. In recent years, increasing evidence has demonstrated that sirtuins are protective toward the pathological process of SCI through a variety of antioxidant mechanisms. Notably, strategies that modulate the expression of sirtuins exert beneficial effects in cellular and animal models of SCI. Given the significance and novelty of sirtuins, we summarize the oxidative stress processes that occur in SCI and discuss the antioxidant effects of sirtuins in SCI. We also highlight the potential of targeting sirtuins for the treatment of SCI.

Deciphering Pharmacological Mechanism of Buyang Huanwu Decoction for Spinal Cord Injury by Network Pharmacology Approach.

OBJECTIVE: The purpose of this study was to investigate the mechanism of action of the Chinese herbal formula Buyang Huanwu Decoction (BYHWD), which is commonly used to treat nerve injuries, in the treatment of spinal cord injury (SCI) using a network pharmacology method. METHODS: BYHWD-related targets were obtained by mining the TCMSP and BATMAN-TCM databases, and SCI-related targets were obtained by mining the DisGeNET, TTD, CTD, GeneCards, and MalaCards databases. The overlapping targets of the abovementioned targets may be potential therapeutic targets for BYHWD anti-SCI. Subsequently, we performed protein-protein interaction (PPI) analysis, screened the hub genes using Cytoscape software, performed Gene Ontology (GO) annotation and KEGG pathway enrichment analysis, and finally achieved molecular docking between the hub proteins and key active compounds. RESULTS: The 189 potential therapeutic targets for BYHWD anti-SCI were overlapping targets of 744 BYHWD-related targets and 923 SCI-related targets. The top 10 genes obtained subsequently included AKT1, IL6, MAPK1, TNF, TP53, VEGFA, CASP3, ALB, MAPK8, and JUN. Fifteen signaling pathways were also screened out after enrichment analysis and literature search. The results of molecular docking of key active compounds and hub target proteins showed a good binding affinity for both. CONCLUSION: This study shows that BYHWD anti-SCI is characterized by a multicomponent, multitarget, and multipathway synergy and provides new insights to explore the specific mechanisms of BYHWD against SCI.

Risk Factors and a New Prediction Model for Pancreatic Fistula After Pancreaticoduodenectomy.

AIM: In order to find the risk factors of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) according to the latest definition and grading system of International Study Group of Pancreatic Surgery (ISGPS) (version 2016) and propose a nomogram for predicting POPF. METHODS: We conducted a retrospective analysis of 232 successive cases of PD performed at our hospital by the same operator from August 2012 to June 2020. POPF was diagnosed in accordance with the latest definition of pancreatic fistula from the ISGPS. The risk factors of POPF were analyzed by univariate and multivariate logistic regression analysis. A nomogram model to predict the risk of POPF was constructed based on significant factors. RESULTS: There were 18 cases of POPF, accounting for 7.8% of the total. Among them, 17 cases were classified into ISGPF grade B and 1 case was classified into ISGPF grade C. In addition, 35 cases were classified into biochemical leak. Univariate and multivariate analysis showed that hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Based on significant factors, a nomogram is plotted to predict the risk of POPF. The C-index of this nomogram to assess prediction accuracy was 0.916 (P < 0.001) indicating good prediction performance. CONCLUSION: Hypertension, non-diabetes, no history of abdominal surgery, antecolic gastrojejunostomy and soft pancreas were independent risk factors of POPF. Meanwhile, a nomogram for predicting POPF with good test performance and discriminatory capacity was constituted.

Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology.

OBJECTIVE: The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. METHODS: In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. RESULTS: 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. CONCLUSION: This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

Distribution and imaging characteristics of spina bifida occulta in young people with low back pain: a retrospective cross-sectional study.

PURPOSE: Spina bifida occulta (SBO) is one of the most common congenital spinal deformities. Although many studies have demonstrated the influence of lumbosacral dysplasia on low back pain (LBP) in young athletes, there have been few studies on SBO among young people in other occupations. The purpose of this study is to investigate the distribution of SBO in young people with LBP and to classify SBO from the perspective of lamina development. METHODS: The X-ray films of 148 young patients with LBP were analyzed to quantify the distribution of SBO and classify abnormal laminae. RESULTS: Of the 148 patients, 93 (61.49%) had SBO: 83 cases involved S1 alone, 2 involved L5-S1, 5 involved S1-2, 2 involved S1-4, and 1 involved L4-S4. According to the degree of the defect, the patients with SBO were divided on the basis of five grades: 9 patients with grade I, 53 with grade II, 23 with grade III, and 8 with grade IV. The cases were classified by the shape of the laminae into 4 types: 15 cases of type a, 11 cases of type b, 37 cases of type c, and 30 cases of type d. CONCLUSION: Among the young people with LBP that we surveyed, SBO is the most common lumbosacral dysplasia, which frequently involves the S1 segment. Most laminae in SBO are in the developmental stage of the spinous process, and an abnormal laminar growth direction and laminar stenosis are the most common laminar morphologies in SBO.

Management of Elevated Blood Pressure After Stroke Thrombectomy for Anterior Circulation.

Thrombectomy is superior to intravenous thrombolysis for patients with large vessel occlusion in acute ischemic stroke, but nearly half of the patients still experience poor functional outcomes. Elevated blood pressure (BP) is widely observed in acute ischemic stroke, and BP may be one of the modifiable parameters that can potentially influence the outcomes; however, only observational studies exist to support current guidelines, and the recommended range for BP after thrombectomy is too wide to meet the clinical requirement. Randomized controlled trials are therefore needed to better understand the relationship between BP and outcomes after thrombectomy. In this review, we introduce the current management of BP after thrombectomy and several aspects of postthrombectomy BP management that should be resolved in future clinical trials.

Extracorporeal shock wave therapy versus local corticosteroid injection for the treatment of carpal tunnel syndrome: a meta-analysis.

BACKGROUND: Many studies have demonstrated the effectiveness of extracorporeal shock wave therapy (ESWT) and local corticosteroid injection (LCI) for the treatment of carpal tunnel syndrome (CTS), and some studies showed that the effect of ESWT was superior to LCI. We performed this meta-analysis to compare the clinical effects across the two therapies. METHODS: Relevant randomized controlled trials (RCTs) comparing ESWT and LCI for the treatment of CTS were searched in electronic database. The Cochrane risk bias tool was used for quality assessment. After data extraction and quality assessment of the included studies, a meta-analysis was performed using RevMan 5.3 software. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were analyzed. The protocol for this systematic review was registered on INPLASY (202080025) and is available in full on the inplasy.com ( https://doi.org/10.37766/inplasy2020.8.0025 ) RESULTS: A total of 5 RCT studies with 204 patients were included from the electronic database. The meta-analysis results showed that two therapies were not significantly different in terms of visual analog scale (VAS) score (P = 0.65), Boston Carpal Tunnel Questionnaire (BQ) score (P = 0.14), sensory distal latency (P = 0.66), and nerve conduction velocity (NCV) of the sensory nerve (P = 0.06). There were significant differences between the results of motor distal latency (P < 0.0001), compound muscle action potential (CMAP) amplitude (P < 0.00001), and sensory nerve action potential (SNAP) amplitude (P = 0.004). CONCLUSIONS: In terms of pain relief and function improvement, the effects of ESWT and LCI are not significantly different. In terms of electrophysiological parameters, LCI has a stronger effect on shortening motor distal latency; ESWT is superior to LCI in improving action potential amplitude. ESWT is a noninvasive treatment with fewer complications and greater patient safety. In light of the heterogeneity and limitations, these conclusions require further research for definitive conclusions to be drawn.

Rebamipide with Proton Pump Inhibitors (PPIs) versus PPIs Alone for the Treatment of Endoscopic Submucosal Dissection-Induced Ulcers: A Meta-analysis.

OBJECTIVE: To contrast the effect of rebamipide with proton pump inhibitors (PPIs) versus PPIs alone for the treatment of endoscopic submucosal dissection (ESD-) induced ulcers. METHODS: PubMed, Embase, the Cochrane library, the WanFang database, and China National Knowledge Infrastructure (CNKI) were searched to identify studies that met the inclusion criteria. RESULTS: Nine randomized controlled trials (RCTs) were recognized, including 1170 patients. In general, rebamipide plus PPIs acted better than PPIs alone against ESD-induced ulcers at four weeks (RR = 1.42, 95% CI: 1.13-1.78, P = 0.003) but showed no significant differences at eight weeks (RR = 1.03, 95% CI: 0.97-1.10, P = 0.315). The use of rebamipide plus PPIs was superior to PPIs alone for ESD-induced ulcers greater than 20 mm in size (20-40 mm: RR = 1.98, 95% CI: 1.22-3.23, P = 0.006; >40 mm: RR = 5.14, 95% CI: 1.49-17.74, P = 0.010). In addition, rebamipide plus PPI therapy was discovered to be significantly more effective than PPIs alone for lower ESD-induced ulcers (RR = 1.82, 95% CI: 1.04-3.20, P = 0.037). There were no significant differences between the treatment groups with the ulcer reduction rate. CONCLUSION: Evidences now available show rebamipide plus PPIs is practical for protecting against ESD-induced ulcers at four weeks but not at eight weeks, especially large ulcers (>20 mm). However, we still need more high-quality RCTs in the future to supplement our conclusions.